Multimodal In Vivo Imaging of Tumorigenesis and Response to Chemotherapy in a Transgenic Mouse Model of Mammary Cancer

• Published in: Molecular imaging and biology 2016-08, Vol.18 (4), p.617-626
• Main Authors: Alberini, Jean-Louis, Boisgard, Raphaël, Guillermet, Stéphanie, Siquier, Karine, Jego, Benoît, Thézé, Benoît, Urien, Saik, Rezaï, Keyvan, Menet, Emmanuelle, Maroy, Renaud, Dollé, Frédéric, Kühnast, Bertrand, Tavitian, Bertrand
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Bioengineering; Cancer; Carcinogenesis - pathology; Cell Proliferation; Disease Models, Animal; Disease Progression; Female; Fluorescence; Fluorodeoxyglucose F18; Imaging; Ki-67 Antigen - metabolism; Life Sciences; Mammary Neoplasms, Animal - blood supply; Mammary Neoplasms, Animal - diagnostic imaging; Mammary Neoplasms, Animal - drug therapy; Mammary Neoplasms, Animal - pathology; Medicine; Medicine & Public Health; Mice; Mice, Transgenic; Multimodal Imaging - methods; Pharmaceutical sciences; Pharmacology; Radiology; Research Article; Technetium - chemistry; Time Factors; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
• ISSN: 1536-1632; 1860-2002
• DOI: 10.1007/s11307-015-0916-7

Purpose Transgenic mice expressing the polyoma middle T oncoprotein (PyMT) in the mammary epithelium were explored by multimodal imaging to monitor longitudinally spontaneous tumor growth and response to chemotherapy. Procedures Positron emission tomography (PET) with 2-deoxy-2-[ 18 F]fluoro- d -glucose ([ 18 F]FDG) and 3'-deoxy-3'-[ 18 F]fluorothymidine ([ 18 F]FLT), single photon emission tomography (SPECT) with [ 99m Tc]TcO 4 ([ 99m Tc]TEC), X-ray computed tomography, and fluorescent confocal endomicroscopy (FCE) images were acquired during tumor progression in female PyMT mice. Imaging with [ 18 F]FDG and [ 99m Tc]TEC was also performed in untreated, doxorubicin-treated, and docetaxel-treated PyMT mice. Total tumor volumes were quantified. Tumors were collected and macroscopic and histological examinations were performed. Results All PyMT mice developed multifocal tumors of the mammary epithelium that became palpable at 8 weeks of age (W8). Computed tomography (CT) detected tumors at W14, while a clear tumoral uptake of [ 99m Tc]TEC and [ 18 F]FDG was present as early as W6 and W8, respectively. No contrast between mammary tumors and surrounding tissue was observed at any stage with [ 18 F]FLT. FCE detected an angiogenic switch at W10. Lung metastases were not clearly evidenced by imaging. Doxorubicin and docetaxel treatments delayed tumor growth, as shown by [ 18 F]FDG and [ 99m Tc]TEC, but tumor growth resumed upon treatment discontinuation. Tumor growth fitted an exponential model with time constant rates of 0.315, 0.145, and 0.212 week −1 in untreated, doxorubicin, and docetaxel groups, respectively. Conclusions Molecular imaging of mammary tumors in PyMT is precocious, precise, and predictive. [ 18 F]FDG-PET and [ 99m Tc]TEC SPECT monitor tumor response to chemotherapy.